Biological assessment and human absorbed dose estimation of [111In]In-DTPA-antiMUC1 as a radioimmunoconjugate for breast cancer imaging

Document Type : Original Article


1 Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran

2 Material and Nuclear Fuel Research School, Nuclear Science and Technology Research Institute, Tehran, Iran


Introduction: The aim of this study was to evaluate the human organ absorbed dose of [111In]In-DTPA-antiMUC1, as a newly developed radioimmunoconjugate.
Methods: [111In]In-DTPA-antiMUC1 was prepared at optimized conditions while the radiochemical purity of the tracer was investigated using ITLC method. Biodistribution of the radiolabeled complex was assessed in tumor bearing BALB/c mice and the human absorbed dose of the radiotracer was estimated based on the gathered data in animals according to the standard methods.
Results: The highest absorbed dose is observed in the spleen and the liver with 0.112 and 0.087 mGy/MBq, respectively. In addition, the estimated human equivalent and effective absorbed dose were 0.008 mGy/MBq and 0.041 mSv/MBq, respectively.
Conclusion: [111In]In-DTPA-antiMUC1 radioimmunoconjugate can be considered as an effective and safe radiolabeled compound for MUC1 positive breast cancer SPECT imaging.


Main Subjects

  1. Clarke CA, Glaser S, West DW, Ereman RP, Erdmann CA, Barlow JM, Wrensch MR. Breast cancer incidence and mortality trends in affluent population: marin county, California, USA, 1990-1999. Breast Cancer Res. 2002 Jul;4(6):R13.
  2. Rabie A, Yousefnia H, Zolghadri S, Shamsaei M, Jalilian AR. Preparation, quality control and biodistribution study of 68Ga-BPAMD: Optimized production with an in-house 68Ge-68Ga generator. Iran J Nucl Med. 2018;26(2): 82-6.
  3. Signore A, Lauri C, Auletta S, Varani M, Onofrio L, Glaudemans AWJM, Panzuto F, Marchetti P. Radiopharmaceuticals for Breast Cancer and Neuroendocrine Tumors: Two Examples of How Tissue Characterization May Influence the Choice of Therapy. Cancers (Basel). 2020 Mar 25;12(4):781.
  4. Sharifi M , Yousefnia H, Bahrami-Samani  A, Jalilian AR , Zolghadri S , Alirezapour B , Geramifar P , Maus S, Beiki D. Optimized production, quality control, biological evaluation and PET/CT imaging of 68Ga-PSMA-617 in breast adenocarcinoma model. Radiochim Acta. 2017;105(5):399-407.
  5.  Zolghadri S, Naderi M, Yousefnia H, Alirezapour B, Beiki D. Evaluation of the Possible Utilization of 68Ga-DOTATOC in Diagnosis of Adenocarcinoma Breast Cancer. Asia Ocean J Nucl Med Biol. 2018 Winter;6(1):41-49.
  6. Vahidfar N, Aghanejad A, Ahmadzadehfar H, Farzanehfar S, Eppard E. Theranostic Advances in Breast Cancer in Nuclear Medicine. Int J Mol Sci. 2021;22(9):4597.
  7. Paknejad M, Rasaee MJ, Tehrani FK, Kashanian S, Mohagheghi MA, Omidfar K, Bazl MR. Production of monoclonal antibody, PR81, recognizing the tandem repeat region of MUC1 mucin. Hybrid Hybridomics. 2003 Jun;22(3):153-8.
  8. Salouti M, Babaei MH, Rajabi H, Foroutan H, Rasaee MJ, Rajabi AB, Mohammadnejad J, Shafiee M, Mazidi M, Daha FJ. Comparison of (99m)Tc-labeled PR81 and its F(ab')₂ fragments as radioimmunoscintigraphy agents for breast cancer imaging. Ann Nucl Med. 2011 Feb;25(2):87-92.
  9. Salouti M, Babaei MH, Rasaee MJ. Breast tumor targeting with 99mTc-HYNIC-PR81 complex as a new biologic radiopharmaceutical. Nucl Med Biol. 2008 Oct;35(7):763-768.
  10. Mohammadnejad J, Rasaee MJ, Babaei MH, Paknejad M, Hasan ZM, Salouti M, Gandomkar M, Sadri K. Radioimmunotherapy of MCF7 breast cancer cell line with 131I-PR81 monoclonal antibody against MUC1: comparison of direct and indirect radioiodination methods. Hum Antibodies. 2010;19(1):15-25.
  11. Salouti M, Babaei MH, Rajabi H, Rasaee MJ. Preparation and biological evaluation of (177)Lu conjugated PR81 for radioimmunotherapy of breast cancer. Nucl Med Biol. 2011 Aug;38(6):849-55.
  12. Alirezapour B, Rasaee MJ, Jalilian AR, Rajabifar S, Mohammadnejad J, Paknejad M, Maadi E, Moradkhani S. Development of [64Cu]-DOTA-PR81 radioimmunoconjugate for MUC-1 positive PET imaging. Nucl Med Biol. 2016 Jan;43(1):73-80.
  13. Abbas Abadi S, Alirezapour B, Kertész I, Rasaee MJ, Mohammadnejad J, Paknejad M, Yousefnia H, Zolghadri S.   Preparation, quality control, and biodistribution assessment of [111In]In-DOTA-PR81 in BALB/c mice bearing breast tumors. J Labelled Comp Radiopharm. 2021 April; 64(4):168-80.
  14. Sadeghi M, Karami H, Sarabadani P, Bolourinovin F. Separation of the no-carrier-added 109Cd from Ag, Cu and 65Zn by use of a precipitation and AG1-X8 resin.   J Radioanal Nucl Chem. 2009 Sep; 281(3): 619–23.
  15. Jalilian A, Yousefnia H , Zolghadri S, Khoshdel M, Bolourinovin F, Rahiminejad A. Development of radiogallium–ethylenecysteamine cysteine complex as a possible renal imaging agent.  J Radioanal Nucl Chem. 2010 Apr;284(1): 49-54.
  16. Table of isotopes decay data. Available at: “”
  17. Stabin MG, Tagesson M, Thomas SR, Ljungberg M, Strand SE. Radiation dosimetry in nuclear medicine. Appl Radiat Isot. 1999 Jan;50(1):73-87.
  18. Stabin MG, Siegel JA. Physical models and dose factors for use in internal dose assessment. Health Phys. 2003 Sep;85(3):294-310.
  19. Shanehsazzadeh S, Yousefnia H, Jalilian AR, Zolghadri S, Lahooti A. Estimated human absorbed dose for 68Ga-ECC based on mice data: comparison with 67Ga-ECC. Ann Nucl Med. 2015 Mar; 29:475–81.
  20. Yousefnia H, Zolghadri S, Shanehsazzadeh S. Estimated human absorbed dose of 177Lu–BPAMD based on mice data: Comparison with 177Lu–EDTMP. Appl Radiat Isot. 2015 Oct; 104: 128-35.
  21. Yousefnia H, Jalilian AR, Zolghadri S, Mirzaei A, Bahrami-Samani A, Mirzaii M,  Ghannadi M. 2015. Development of 111In DOTMP for dosimetry of bone pain palliation agents. J Radioanal Nucl Chem. 2015 Jan;304:911–6.
  22. Mirzaii M, Seyyedi S, Sadeghi M, Gholamzadeh Z. Cadmium electrodeposition on copper substrate for cyclotron production of 111In radionuclide.  J Radioanal Nucl Chem. 2010 May; 284(2): 333–9.
  23. IAEA-TECDOC-1401.Quantifying uncertainty in nuclear analytical measurements. Austria, Vienna: IAEA; 2004.
  24. Sparks RB, Aydogan B. Comparison of the effectiveness of some common animal data scaling techniques in estimating human radiation dose. Proceedings of the Sixth International Radiopharmaceutical Dosimetry Symposium; 1996 May 705-16; Gatlinburg, Tennessee.
  25. Yousefnia H, Zolghadri S, Jalilian AR, Tajik M, Ghannadi-Maragheh M. Preliminary dosimetric evaluation of (166)Ho-TTHMP for human based on biodistribution data in rats. Appl Radiat Isot. 2014 Dec;94:260-5.
  26. Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: The second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005 Jun;46(6):1023-7.
  27. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP. 2007;37(2-4):1-332.
  28. Kesner AL, Hsueh WA, Czernin J, Padgett H, Phelps ME, Silverman DH. Radiation dose estimates for [18F]5-fluorouracil derived from PET-based and tissue-based methods in rats. Mol Imaging Biol. 2008 Nov-Dec;10(6):341-8.
  29. Radiological protection in biomedical research: ICRP Publication 62. Ann ICRP. 1992;22(3).
  30. Gaykema SB, de Jong JR, Perik PJ, Brouwers AH, Schröder CP, Oude Munnink TH, Bongaerts AH, de Vries EG, Lub-de Hooge MN. (111)In-trastuzumab scintigraphy in HER2-positive metastatic breast cancer patients remains feasible during trastuzumab treatment. Mol Imaging. 2014;13(5).
  31. Bombardieri E, Ambrosini V, Aktolun C, Baum RP, Bishof-Delaloye A, Del Vecchio S, Maffioli L, Mortelmans L, Oyen W, Pepe G, Chiti A. 111In-pentetreotide scintigraphy: procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging. 2010 Jul;37(7):1441-8.
  32. Mankoff DA, Peterson LM, Tewson TJ, Link JM, Gralow JR, Graham MM, Krohn KA. [18F]fluoroestradiol radiation dosimetry in human PET studies. J Nucl Med. 2001 Apr;42:679-84.
  33.  McCall K, Abbott A, Hu J, Cheng SC, Kravets S, Dubey S. Report on the PET/CT image-based radiation dosimetry of 18FDHT in women, an imaging agent with new applications for evaluation of androgen receptor status in patients with metastatic breast cancer. J Nucl Med. 2019 May;60:1630.